A MODEL OF PARASAGITTAL CONTROLLED CORTICAL IMPACT IN THE MOUSE - COGNITIVE AND HISTOPATHOLOGIC EFFECTS

Controlled cortical impact (CCI), using a pneumatically driven impacto r to produce traumatic brain injury, has been characterized previously in both the ferret and in the rat. In the present study, we applied t his technique to establish and characterize the CCI model of brain inj ury in another species, the mouse, evaluating cognitive and histopatho logic outcome. In anesthetized (sodium pentobarbital, 65 mg/kg) male C 57BL mice, we performed sham treatment (no injury, n = 12) or CCI inju ry (n = 12) at a velocity of 5.7-6.2 m/sec and depth of 1 mm, using a 3-mm diameter rounded-tip impounder, positioned over the left parietot emporal cortex (parasagittal). At this level of injury, we observed hi ghly significant deficits in memory retention of a Morris water maze t ask 2 days following injury (p < 0.001). Postmortem histopathologic an alysis performed at 48 h following injury revealed substantial cortica l tissue loss in the region of impact and selective hippocampal neuron al cell loss in the CA2, CA3, and CA3c regions, using Nissl staining. Analysis of degenerating neurons using modified Gallyas silver stainin g techniques demonstrated consistent ipsilateral injury of neurons in the cortex adjacent to the impact site and in the dentate gyrus of the ipsilateral hippocampus. Bilateral degeneration was observed at the g ray matter-white matter interface along the corpus callosum. Glial fib rillary acidic protein (GFAP) immunohistochemistry revealed extensive reactive gliosis appearing diffusely through the bilateral cortices, h ippocampi, and thalami at 48 h postinjury. Breakdown of the blood-brai n barrier was demonstrated with antimouse IgG immunohistochemistry, re vealing extravasation of endogenous IgG throughout the ipsilateral cor tex, hippocampus, and thalamus. These results suggest that this new mo del of parasagittal CCI in the mouse mimics a number of well-establish ed sequelae observed in previously characterized brain injury models u sing other rodent species. This mouse model may be a particularly usef ul experimental tool for comparing behavioral and histopathologic char acteristics of traumatic brain injury in wild-type and genetically alt ered mice.